The direct catalytic asymmetric cross-Mannich reaction: A highly enantioselective route to 3-amino alcohols and amino acid derivatives

ORGN 474

Armando Córdova and Henrik Sundén. Department of Organic Chemistry, Stockholm University, The Arrhenius Laboratory, Stockholm, 106 91, Sweden
In this paper, we disclose the first proline-catalyzed direct catalytic asymmetric one-pot three-component cross-Mannich reaction. The highly chemoselective reactions between two different unmodified aldehydes and one aromatic amine are new routes to 3-amino aldehydes with dr >19:1 and up to >99% ee. The asymmetric cross-Mannich reactions are highly syn-selective and in several cases the two new carbon centers are formed with complete stereocontrol. The reaction does not display non-linear effects and therefore only one proline molecule is involved in the transition-state. The reaction was also catalyzed by other proline-derivatives with good selectivity. The Mannich products were converted to amino alcohols and 2-aminobutane-1, 4-diols with up to >99% ee. The one-pot three component direct catalytic asymmetric reactions were readily scaled-up, operationally simple and conducted in environmentally benign and wet solvents. The mechanism and stereochemistry of the proline-catalyzed one-pot three-component asymmetric cross-Mannich reaction are also discussed.
 

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, March 29, 2004 Anaheim Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004